The formation and maintenance of a proper soft-tissue seal, or interface region, is essential to the success of over 800,000 percutaneous medical devices implanted annually in the United States. Due to the prevalence of percutaneous devices in contemporary medicine along with the growing reliance on technologically advanced treatment delivery systems, exponential growth is expected in the number of patients who will undergo procedures involving percutaneous devices. It can be assumed that as the number of devices in use grows, so too will the number of failures, leading to increases in medical cost and a negative impact on patient quality of life. Despite great advances in the family of percutaneous medical devices there still exist profound limitations, many of which are exacerbated by the disintegration of a soft- tissue to device interface. The chief interface region failure modality of percutaneous devices is exit-site epidermal regression. This regression is the product of the disruptions of the mechanical behavior of the whole tissue and individual cells due to changes in the mechanical integrity of their environment. Exit-site epidermal regression leads to various types of infections. Due to the exposure of underlying tissue in these systems, any infection poses a significant risk to the well-being of the patient. It is my hypothesis that, to avoid epidermal regression, it is necessary to develop an accurate way to describe, then minimize, the contribution of micro-strain, shear induced stress concentrations to changes in the physiologic/metabolic processes that lead to tissue degradation. Once an accurate means for analyzing the stress concentrations in the interface region have been developed, a vibration/stress isolating system aimed at reducing those localized stresses will be designed and tested- both computationally and empirically. To test this hypothesis, I propose a three phase investigation of the current osseointegrated lower-limb prosthetic: 1) a detailed viscoelastic characterization of human skin and development of a unique mathematical model to describe the behavior of living human skin under shear; 2) the creation of a finite element model for optimization of the system; and 3) in vitro experimentation with a prototype of the optimized percutaneous prosthetic system and bioengineered skin. [unreadable] [unreadable] [unreadable]